Which risk assessment strategy to initiate primary prevention therapy prevents most ASCVD events?


Literature - Mortensen MB et al., JACC 2015

Primary Prevention With Statins: ACC/AHA Risk-Based Approach Versus Trial-Based Approaches to Guide Statin Therapy

Mortensen MB, Afzal S, Nordestgaard BG et al.
JACC 2015;66(24):2699-709.Guidelines for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) currently recommend the use of absolute risk prediction to guide statin prescription (1–3). The calculation of absolute risk is based on selected data that were generated decades ago. The appropriateness of this recommendation has been questioned because (4,5): patients are not enrolled in statin randomized clinical trials (RCTs) based on their predicted 10-year ASCVD risk, and absolute risk prediction has never been clinically evaluated in primary prevention. 
Therefore, alternative approaches to guide statin prescription in the primary prevention setting have been proposed.
  • The ’’trial-based’’ method suggests that only patients who had a benefit from statin therapy in RCTs should receive this therapy in primary prevention, irrespective of their individual risk assessment (6,7).
  • According to the hybrid approach, the allocation of statins in primary prevention should be based on a combination of the ‘’trial-based’’ method and the absolute ASCVD risk assessment (8).
In the present study, the ACC/AHA risk-based approach was compared to the ‘’trial-based’’ method and the ‘’hybrid approach’’, in an ongoing prospective cohort study, the Copenhagen General Population Study (9). Participants were enrolled between 2003 and 2008, and aged 40-75 years. All 37,892 subjects (57% females) had no history of diabetes, ASCVD, or statin use at baseline. During follow-up (182,641 person-years), 834 developed ASCVD, and 323 ASCVDs were myocardial infarctions.  

Main results

Statin eligibility
  • According to the trial-based approach, more individuals were eligible for statin therapy, compared with the ACC/AHA risk-based approach (56% vs. 42%; p<0.0001). This finding was observed in both women (49% vs. 29%; P<0.0001) and men (67% vs. 60%; P<0.0001).
  • According to the hybrid approach, fewer individuals were eligible for statin therapy, compared to the ACC/AHA approach (21% vs. 42%; P<0.0001). 30% of men and 14% of women were eligible for statin therapy with the hybrid approach.
  • Among individuals who were eligible for statin therapy with the ACC/AHA approach, 20% were not eligible for statin therapy with the hybrid approach.
  • Among those who qualified for statin treatment according to the trial-based approach, 68% of women and 32% of men had a 10-year ASCVD risk <7.5%, disqualifying them under the ACC/AHA approach.
  • Of those eligible for statin therapy, the ASCVD event rate per 1,000 person-years was 9.8 (95%CI: 9.1-10.6), with the ACC/AHA approach 6.8 (95%CI: 6.3-7.4), with the trial-based approach and 11.2 (95%CI:10.1-12.5) with the hybrid approach.
Calibration, discrimination, and clinical performance
  • The 10-year ASCVD risk was overestimated by the ACC/AHA risk score in subjects with relatively high risk (>10% 10-year ASCVD risk). Calibration was good around the 7.5% treatment threshold (predicted/observed ratios ranging from 1.1. to 1.2).
  • The ACC/AHA Class I recommendations for statin therapy discriminated much better between individuals who did suffer an ASCVD during follow-up and those who did not, compared to the RCTs enrolment criteria with statins, or according to the hybrid approach treatment criteria. The area under the receiver-operating curve was 0.676 for the ACC/AHA approach, 0.572 for the trial-based approach and 0.613 for the hybrid approach (P<0.0001).
  • In men, sensitivity and specificity were higher with the ACC/AHA approach compared to the trial-based approach. In women, only specificity was higher.
    The hybrid approach had a lower sensitivity and a higher specificity compared to the ACC/AHA approach.


In an ongoing prospective cohort study, examining three different methods to guide statin therapy in a primary ASCVD prevention setting, the ACC/AHA approach was superior to the trial-based approach, indicating that more ASCVD events can be prevented by treating fewer subjects when using the ACC/AHA approach. The use of the hybrid approach decreased the number of subjects eligible for statin therapy significantly in this setting, but the balance between sensitivity and specificity still favoured the ACC/AHA risk-based approach. 

Find this article online at JACC


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8. Ridker PM, Rose L, Cook NR. A Proposal to incorporate trial data into a hybrid ACC/AHA algorithm for the allocation of statin therapy in primary prevention. J Am Coll Cardiol 2015;65:942–8.
9. Mortensen MB, Afzal S, Nordestgaard BG et al. The high-density lipoprotein-adjusted SCORE model worsens SCORE-based risk classification in a contemporary population of 30 824 Europeans: the Copenhagen General Population Study. Eur Heart J 2015;36:2446–53.

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